CARBONIC-ANHYDRASE ACTIVATORS .15. A KINETIC-STUDY OF THE INTERACTIONOF BOVINE ISOZYME-II WITH PYRAZOLES, BIS-AZOLYL-METHANE AND TRIS-AZOLYL-METHANE

A series of eighteen substituted pyrazoles, bis- and tris-azolyl-metha nes or ethanes was investigated for their interaction with the zinc en zyme carbonic anhydrase (CA). Several types of activities mere detecte d, generally as CA activators, but CA inhibitory properties were also discovered for the very sterically-demanding derivatives of these seri es. Kinetic determinations by a stopped-flow technique for carbon diox ide hydration reaction allowed the determination of Michaelis-Menten c onstants, which are identical in the absence or in the presence of the se modulators, proving a noncompetitive mechanism of activation-inhibi tion. MNDO calculations were used with moderate success to explain the biological results.